Antibodies have emerged as effective tools in the treatment of variety of conditions including cancer, inflammation, and other diseases. However, non-human antibodies have been demonstrated to induce human immune responses, which results in neutralization of administered antibody and limits the application of such antibodies in treatment of human diseases. The art has attempted to overcome this problem by humanizing monoclonal antibodies derived from non-human animals, e.g., mice and rabbit. For example, a humanized antibody can be accomplished by grafting the appropriate complementary determining region (CDR) coding segments into a human antibody framework. However, antibodies humanized by CDR graft method often have problem of loss of affinity to their specific targets.
T cell receptor (TCR) is a molecule found on the surface of T cells that is responsible for recognizing antigens bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen is of relatively low affinity and is degenerate, i.e., many TCRs recognize the same antigen and many antigens are recognized by the same TCR. The affinity of TCR or a specific antigen makes them valuable for therapeutic uses, e.g., cancer treatment by using adoptive immunotherapy. In order to extend the capacity to use adoptive immunotherapy, it is a goal to transfer enriched, peptide-specific effector T cells that have been selected for their ligand specificities to effectively attack tumor cells which avoiding serious attach of normal tissues. For this purpose, the TCRs of such ligand-specific T cells can be cloned and expressed as TCR-transgenes in activated T cells, such that the transgenic T cells obtain defined specificities and do not have the capacity to attack normal host tissues.
Therefore, there is a continuing need for new method to develop antibodies and T cell receptors.